Single-Domain Claudin-6 Binders for Solid Tumor CAR-T Targeting

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Solution Overview

Problem

There is a need for new anti-Claudin-6 binders and immunotherapies, such as CAR-T therapies, to target Claudin-6, which is highly expressed in certain solid tumors and associated with cancer progression and drug resistance.

Innovation Solution

Development of anti-Claudin-6 single domain antibodies (sdAbs) with specific CDR sequences and chimeric antigen receptors (CARs) that target Claudin-6 and/or GPC3, combined with engineered immune cells, to treat Claudin-6 and GPC3 associated diseases like solid tumors.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If traditional antibodies are used to target Claudin-6, then antigen binding capability is achieved, but molecular weight is large and tissue penetration is poor

Engineering Contradiction:

Improvemolecular weightVSAvoidtissue penetration capability

Core Design Contradiction:

Quantity of substanceVSReliability

Solution Approach 1:

The patent extracts only the essential antigen-binding domain (variable region) from the complete antibody molecule to create single-domain antibodies. This extraction reduces molecular weight from approximately 150 kDa to about 15 kDa while preserving the ability to bind Claudin-6, thereby improving tissue penetration without sacrificing target recognition capability.

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent segments the antibody molecule into independent single-domain units that can function autonomously. These segmented sdAbs can be further assembled into multimeric formats (dimers, trimers, tetramers) to restore effector functions while maintaining small individual unit sizes for better tissue penetration.

Inventive Principle:

Principle #1Segmentation

2Measurement precision

If single domain antibodies are designed with high specificity, then binding affinity is improved, but development time and complexity increase

Engineering Contradiction:

Improvebinding affinityVSAvoiddevelopment time

Core Design Contradiction:

Measurement precisionVSLoss of time

Solution Approach 1:

The patent employs phage display technology where antibody libraries are selected and optimized automatically through multiple rounds of panning against Claudin-6. This self-service selection process identifies high-affinity binders without requiring extensive manual intervention or complex screening procedures, reducing development time while achieving high binding affinity.

Inventive Principle:

Principle #25Self-service

Solution Approach 2:

The patent optimizes specific parameters of the single-domain antibodies including CDR region sequences, framework region compositions, and amino acid substitutions to enhance binding affinity. By systematically adjusting these parameters based on structure-activity relationships, high-affinity binders are obtained more efficiently.

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS20260027209A1Claudin-6 binding moieties and uses thereof

Publication Date: 2026.01.29 LEGEND BIOTECH USA INC

AI summary

Provided are anti-Claudin-6 antibodies (e.g., VHH domain antibodies), and a chimeric antigen receptor (CAR) that binds to Claudin-6 comprising same in an extracellular antigen binding domain, a transmembrane domain, and an intracellular signaling domain. Immune effector cells transduced with the disclosed CAR constructs can be used for cancer immunotherapy.